1. Field of the Invention
This invention relates generally to an implantable medical device; and more particularly to an implantable stent.
2. Discussion of the Prior Art
Damage to the endothelial and medial layers of a blood vessel, such as often occurs in the coarse of balloon angioplasty and stent procedures, has been found to stimulate neointimal proliferation, leading to restenosis of atherosclerotic vessels.
The normal endothelium, which lines blood vessels, is uniquely and completely compatible with blood. Endothelial cells initiate metabolic processes, like the secretion of prostacylin and endothelium-derived relaxing factor (EDRF), which actively discourage platelet deposition and thrombus formation in vessel walls. However, damaged arterial surfaces within the vascular system are highly susceptible to thrombus formation. Abnormal platelet deposition, resulting in thrombosis, is more likely to occur in vessels in which endothelial, medial and adventitial damage has occurred. While systemic drugs have been used to prevent coagulation and to inhibit platelet aggregation, a need exists for a means by which a damaged vessel can be treated directly to prevent thrombus formation and subsequent intimal smooth muscle cell proliferation.
Current treatment regimes for stenosis or occluded vessels include mechanical interventions. However, these techniques also serve to exacerbate the injury, precipitating new smooth muscle cell proliferation and neointimal growth. For example, stenotic arteries are often treated with balloon angioplasty, which involves the mechanical dilation of a vessel with an inflatable catheter. The effectiveness of this procedure is limited in some patients because the treatment itself damages the vessel, thereby inducing proliferation of smooth muscle cells and reocclusion or restenosis of the vessel. It has been estimated that approximately 30 to 40 percent of patients treated by balloon angioplasty and/or stents may experience restenosis within one year of the procedure.
To overcome these problems, numerous approaches have been taken to providing stents useful in the repair of damaged vasculature. In one aspect, the stent itself reduces restenosis in a mechanical way by providing a larger lumen. For example, some stents gradually enlarge over time. To prevent damage to the lumen wall during implantation of the stent, many stents are implanted in a contracted form mounted on a partially expanded balloon of a balloon catheter and then expanded in situ to contact the lumen wall. U.S. Pat. No. 5,059,211 discloses an expandable stent for supporting the interior wall of a coronary artery wherein the stent body is made of a porous bioabsorbable material. To aid in avoiding damage to vasculature during implant of such stents, U.S. Pat. No. 5,662,960 discloses a friction-reducing coating of commingled hydrogel suitable for application to polymeric plastic, rubber or metallic substrates that can be applied to the surface of a stent.
A number of agents that affect cell proliferation have been tested as pharmacological treatments for stenosis and restenosis in an attempt to slow or inhibit proliferation of smooth muscle cells. These compositions have included heparin, coumarin, aspirin, fish oils, calcium antagonists, steroids, prostacyclin, ultraviolet irradiation, and others. Such agents may be systemically applied or may be delivered on a more local basis using a drug delivery catheter or a drug eluting stent. In particular, biodegradable polymer matrices containing a pharmaceutical may be implanted at a treatment site. As the polymer degrades, a medicament is released directly at the treatment site. The rate at which the drug is delivered is dependent upon the rate at which the polymer matrix is resorbed by the body. U.S. Pat. No. 5,342,348 to Kaplan and U.S. Pat. No. 5,419,760 to Norciso are exemplary of this technology. U.S. Pat. No. 5,766,710 discloses a stent formed of composite biodegradable polymers of different melting temperatures.
Porous stents formed from porous polymers or sintered metal particles or fibers have also been used for release of therapeutic drugs within a damaged vessel, as disclosed in U.S. Pat. No. 5,843,172. However, tissue surrounding a porous stent tends to infiltrate the pores. In certain applications, pores that promote tissue ingrowth are considered to be counterproductive because the growth of neointima can occlude the artery, or other body lumen, into which the stent is being placed.
Delivery of drugs to the damaged arterial wall components has also been explored by using latticed intravascular stents that have been seeded with sheep endothelial cells engineered to secrete a therapeutic protein, such as t-PA (D. A. Dichek et al., Circulation, 80, 1347–1353, 1989). However, endothelium is known to be capable of promoting both coagulation and thrombolysis.
Another approach to controlling the healing of a damaged artery or vein is to induce apoptosis in neointimal cells to reduce the size of a stenotic lesion. U.S. Pat. No. 5,776,905 to Gibbons et al., which is incorporated herein by reference in its entirety, describes induction of apoptosis by administering anti-sense oligonucleotides that counteract the anti-apoptotic gene, bcl-x, which is expressed at high levels by neointimal cells. These anti-sense oligonucleotides are intended to block expression of the anti-apoptotic gene bcl-x so that the neointimal cells are induced to undergo programmed cell death.
Under certain conditions, the body naturally produces another drug that has an influence on cell apoptosis among its many effects. As is explained in U.S. Pat. No. 5,759,836 to Amin et al., which is incorporated herein by reference in its entirety, nitric oxide (NO) is produced by an inducible enzyme, nitric oxide synthase, which belongs to a family of proteins beneficial to arterial homeostasis.
However, the effect of nitric oxide in the regulation of apoptosis is complex. A pro-apoptotic effect seems to be linked to pathophysiological conditions wherein high amounts of NO are produced by the inducible nitric oxide synthase. By contrast, an anti-apoptotic effect results from the continuous, low level release of endothelial NO, which inhibits apoptosis and is believed to contribute to the anti-atherosclerotic function of NO. Dimmeler in “Nitric Oxide and Apoptosis: Another Paradigm For The Double-Edged Role of Nitric Oxide” (Nitric Oxide 1(4): 275–281, 1997) discusses the pro- and anti-apoptotic effects of nitric oxide.
In many instances it is desirable to prevent neointimal proliferation that leads to stenosis or restenosis. U.S. Pat. No. 5,766,584 to Edelman et al. describes a method for inhibiting vascular smooth muscle cell proliferation following injury to the endothelial cell lining by creating a matrix containing endothelial cells and surgically wrapping the matrix about the tunica adventitia. The matrix, and especially the endothelial cells attached to the matrix, secrete products that diffuse into surrounding tissue, but do not migrate to the endothelial cell lining of the injured blood vessel.
In the treatment of heart disease it is also important to determine the overall effectiveness of the heart as a pump and the ability of the blood vessels to carry blood to other organs. If blood flow to an organ is significantly restricted, the organ can be damaged, and if the flow is stopped, death may occur. Consequently, the measure of the flow of blood within a blood vessel has been used as an indicator of the condition of the blood vessel and the pumping action of the heart. By monitoring the blood flow of a patient, the early detection of a heart condition, or of restenosis, is possible, and preventative measures may be taken to address any problems. If the blood vessel becomes seriously clogged, angioplasty or a by-pass operation may be performed that uses a graft to circumvent the damaged vessel.
In overseeing the condition of a patient's blood vessel, a number of blood flow measurements may be needed, over time, to effectively monitor the patient's condition. One known method of monitoring the flow of blood in a vessel involves the percutaneous application of an instrument to measure the flow. Such methods are termed “invasive” because the body must be pierced to obtain the blood flow measurement. Clearly, invasive techniques to measure blood flow have a disadvantage in that the measurement must be taken under controlled conditions. For example, it is difficult, if not impossible, to monitor blood flow during periods of increased exercise.
Despite the progress of the art in providing implantable stents useful for treating a damaged body lumen, there is a need for new and better stents, particularly for stents that are adapted to promote growth of infiltrating cells into organized cellular structures, such as take place during angiogenesis and/or neovascularization, to aid in repair of a damaged body lumen. It is also apparent that a device that non-invasively measures the flow of blood in a blood vessel is desirable.